Journal
BRAIN RESEARCH
Volume 1305, Issue -, Pages S7-S19Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2009.09.075
Keywords
Nociceptin; NOP receptor; Ro 64-6198; Learning and memory; Mice
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Funding
- Swedish Labour Market Insurance (AFA)
- Funds of Karolinska Institutet
- Marcus and Amalia Wallenberg Foundation
- Swedish Research Council
- Systembolaget AB and Wallenberg Consortium North
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This study examines the effects of NOP agonists nociceptin/orphanin FQ (N/OFQ) and Ro 64-6198, NOP antagonists [Nphe(1)]N/OFQ(1-13)-NH2 Nphe(1) and naloxone benzoylhydrazone (NalBzoH) on spatial memory in NMRI mice and pronociceptin (proNC) knockout (KO) mice using the water maze task. N/OFQ administered i.c.v. (1, 5 and 10 nmol/mouse) and into hippocampal CA3 (1 nmol/mouse, bilaterally), impaired acquisition and retention in the maze. Impairments were blocked by pre-treatment with Nphe(1) (10 nmol, i.c.v..). Ro 64-6198 (0.1-0.3-1 mg/kg i.p.) also dose-dependently impaired learning. However, pre-treatment with NalBzoH (1 mg/kg, S.C.) failed to modify the effects of Ro 64-6198. Nphe(1)(10 nmol/mouse i.c.v.) and NalBzoH (1 mg/kg, S.C.) by themselves failed to affect maze performance, despite a tendency for enhanced performance. Prepro N/OFQ knockout (ppN/OFQ-/-) showed evidence of improved learning, evident at retention trials and in reversal training. ppN/OFQ -/- mice were not impaired by N/OFQ (10 nmol i.c.v.) in the task, suggesting that changes in postsynaptic NOP receptors may occur in such KO mice. It is concluded that N/OFQ and NOP receptors have an important role in hippocampus-dependent spatial learning and memory, probably by modulation of glutamatergic functions. (C) 2009 Elsevier B.V. All rights reserved.
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